Department of Chemistry, D. A. V. (P.G.) College, Dehradun-248 001, Uttarakhand, India E-mail : uktripathi@hotmail.com Department of Chemistry, S.M.S. Govt., Model Science College, Gwalior, Madhya Pradesh, India Department of Chemistry, Bansthali Vidhyapeeth, Tank, Rajasthan, India Manuscript received 17 January 2011, accepted 16 June 2011 We performed 2D QSAR studies upon a series of 78 HEPT analogues, inhibitors of HIV reverse transcriptase; using the QSAR that imply analysis of correlation and multilinear regression; a significant collection of descriptors (lipophilicity, steric parameter, field effect, hydrogen acceptor and hydrogen donor) was used. The best QSAR model with good correlation coefficient (r2 = 0. 792) of high statistical significance ( > 99.9%) well explained the variance in activity. The analysis reveal that R1 should have much saturated carbon with branching, R2 should be bulky with less number of H acceptors and R3 should have less number of Haec in support of biological activity. The presence of X=0 or S is not contributing in biological activity to a significant level.